~ Sep 09 Beyond Colonoscopy to Real Protection

By Julius Goepp, MD

The public has long been led to believe that regular colonoscopy screenings offer virtually foolproof pro-tection from colorectal cancer death--a 90%1 mortality risk reduction according to established medical consensus. The latest research suggests the truth may be far less reassuring.

In one of the largest population studies of its kind,2 involving over 60,000 individuals, colonoscopies failed to detect the majority of cancers on the right side of the colon and nearly one third of cancers on the left side of the colon. This does not mean you should skip regular colonoscopy screening. What it indicates according to the authors of the case-controlled study is that colonoscopies most likely afford only a 60-70% mortality risk reduction.

Given that colorectal cancer is the second leading cause of cancer death in the United States for both men and women,1,3 a renewed focus on prevention will be required to provide adequate protection from colo-rectal cancer death. The good news is that advances in our understanding of the molecular basis of colon cancer have yielded a broad array of nutrient-based preventive strategies--without the need for toxic, potentially debilitating pharmaceutical interventions.

Current Colon Cancer Treatment: Insufficient Progress

The unfortunate reality is that despite aggressive campaigns for earlier detection, too many people have already developed fairly advanced forms of cancer by the time they're diagnosed,4 limiting their options to radical, invasive forms of treatment--painful surgery, chemotherapy, and sometimes radiation therapy. While conventional biomedical science has certainly made notable strides in drug treatment--including 6 new chemotherapy agents in the past 12 years that improve overall survival from less than 9 months to approximately 24 months in patients with advanced cancers5--this is insufficient progress for the growing numbers in the research community and beyond committed to effective disease prevention.

Among them is Dr. Maria Elena Martinez, professor of public health at the University of Arizona at Tucson. "There is convincing evidence from epidemiological and experimental studies that dietary intake is an important etiological [causative] factor in colorectal [cancer]," Martinez says. "The overwhelming evidence indicates that primary prevention of colon cancer is feasible."6

Consensus continues to grow among many experts in the field of biomedical science and oncology that lifelong colon health may be promoted safely, effectively, and naturally, using cutting-edge, low-cost nutritional therapies. According to Dr. Jeremy Johnson of the University of Wisconsin's School of Pharmacy, "The most practical approach to reduce the morbidity and mortality of cancer is to delay the process of carcinogenesis [the process by which normal cells are transformed into cancer cells] through the use of chemopreventive [cancer-fighting] agents. This necessitates that safer compounds, especially those derived from natural sources, must be critically examined for chemoprevention."7

This critical examination of safer compounds to support lasting colon health is well underway. Thanks to an ever-expanding body of research in clinical nutrition, we now have a broad array of advanced, evidence-based approaches--each distinguished by their powerful potential to offset the scourge of colon cancer.

Plant-Based Anticancer Strategies: The Polyphenols

Among the largest groups of plant-based nutrients with demonstrated cancer-fighting potential is the polyphenol family.8 It includes the nutritional sub-groups tannins and flavonoids, compounds found in berries, tea, grapes/wine, olive oil, chocolate/cocoa, walnuts, peanuts, pomegranates, and most other fruits and vegetables.9 Numerous epidemiological studies offer solid evidence that diets rich in polyphenols result in significantly lower incidence for many kinds of cancers--including colon cancer.10,11

The secret to polyphenols' preventive power may lie in their extraordinary ability to check cancer growth at multiple stages in its development--including inception. This gives them a leg up on standard chemotherapy drugs that typically work only at a single point in the cancer cell's life cycle--and always after the cancer has already emerged.

Curcumin gives the Indian spice turmeric its yellow color. It's been used for thousands of years in curries, stews, and other traditional dishes. Its importance in south Asian healing practices, however, is less well known.12 In recent years, curcumin has emerged as a leading cancer fighter.

It boasts a formidable nutritional profile, with antioxidant, antimicrobial, and anti-inflammatory properties. This life-extending triple play ranks curcumin among the polyphenols capable of disrupting colon cancer during multiple developmental phases.13-15 Even after a cancer has started to develop, curcumin may be able to slow or stop tumor growth altogether in two important ways:

It sets in motion a process called apoptosis (programmed cell destruction).16

It blocks a process called angiogenesis--the new blood vessel growth tumors need in order to thrive and spread.13,17

As early as 2001, oncologists observed that curcumin may be a potential third-generation cancer chemo-preventive agent.18

Evidence of that observation continues to mount. Researchers at the American Health Foundation in Valhalla, New York studied rats given either curcumin or a regular diet for up to three weeks, followed by heavy exposure to a chemical known to induce colon cancer.15 After a year of observation, those given curcumin developed significantly fewer colonic malignancies. Even more remarkably, when they were given curcumin after carcinogen exposure, it limited both tumor incidence and growth, corralling the aggressive cancer cells most likely to spread. These results reflect great promise for curcumin not only in colon cancer prevention, but also as a potentially effective treatment.

In lab cultures, curcumin slows and even blocks the growth of colon cancer cells, as demonstrated in an elegantly structured study conducted by Israeli researchers in 2005.19 They looked at the effects--alone and in combination--of curcumin and celecoxib (Celebrex®), a potent prescription anti-inflammatory drug commonly used in cancer treatment. Remarkably, the two compounds worked synergistically, each enhancing the other's benefits.19 This mutually reinforcing effect has critically important implications for possible future treatments: it may spare cancer patients the well-documented and potentially dangerous side effects of celecoxib.20

In yet another astonishing set of findings published by Texas researchers in 2007, curcumin suppressed tumor growth in lab cultures better than oxaliplatin, a standard colon cancer chemotherapy drug.21 As the researchers noted, "This study establishes the comparable or greater growth-inhibitory and apoptotic [cancer cell eliminating] effects of liposomal curcumin with oxaliplatin both in vitro [in lab cultures] and in vivo [in the body] in colorectal cancer."

What You Need to Know: Beyond Colonoscopy to Real Protection

Colon cancer strikes more than a million people every year and is among the leading causes of cancer death.

Many people believe that colonoscopy provides foolproof protection against colorectal cancer death. In reality, colonoscopy screenings may only provide a 60-70% mortality risk reduction.

Nutritional experts believe that prevention of many colon cancers is well within our reach.

Powerful plant-derived polyphenols (such as resveratrol, curcumin, EGCG, and quercetin), omega-3 fatty acids (EPA and DHA), plus vitamins and trace elements (such as vitamins E and D and selenium) significantly reduce cancerous changes in laboratory studies and animal models. Those same benefits are being demonstrated in humans in newly-published findings.

Cancer chemoprevention in the colon by nutritional supplementation, along with other healthy lifestyle choices, should be a major part of any bowel health regimen.

In vivo human studies of curcumin are finally catching up with this impressive store of laboratory data. A group of British oncology researchers is currently investigating ideal doses of curcumin for use in colon cancer treatment.22 They are closely tracking its absorption rate, blood levels, and effects on DNA changes in the malignant cells of patients suffering from advanced colorectal cancer. In a phase I clinical trial published in 2004, they reported that doses as high as 3,600 mg daily for up to four months reduced blood levels of an inflammatory compound associated with cancer by up to 60%--with no risk of side effects at even high doses.23 Another human cancer study found no toxicity associated with curcumin at doses of up to 8,000 mg/day for three months.24

An even more vivid demonstration of curcumin's cancer-fighting potential surfaced in a 2005 study of biopsy tissue taken from patients with colorectal cancer.25 The authors observed that curcumin could reduce DNA mutations associated with malignancy, proving unequivocally that curcumin acts directly upon malignant tissue.

Finally, in 2006, scientists at the Cleveland Clinic looked at patients suffering from familial adeno-matous polyposis (FAP), a hereditary condition in which hundreds of pre-malignant polyps, called adenomas, develop and eventually turn malignant. They discovered that a combination of curcumin and another anti-inflammatory polyphenol called quercetin (see below) could cause these growths to diminish substantially.26

Basing their work on the observation that non-steroidal anti-inflammatory (NSAID) drugs can produce a similar result--but with considerable side effects (like Celebrex®)--the Cleveland Clinic researchers supplemented the FAP patients with 480 mg of curcumin and 20 mg of quercetin orally, three times a day, for six months. Every single patient experienced a remarkable decrease in polyp numbers and size, with average reductions of 60% and 51%, respectively!

Advanced clinical trials are now underway to document curcumin's effects in treating and preventing colon cancer in other kinds of patients as well.

Resveratrol

Resveratrol's health-promoting reputation has extended far beyond the research community. It has been broadly publicized and endorsed in the mainstream, from Oprah Winfrey and Dr. Oz to 60 Minutes.

Interestingly, resveratrol evolved in plants as a natural antibacterial agent. It's found in many fruits and berries, including grapes, blueberries, and plums. Most famously, it appears in high concentrations in red wine. Its potent preventive action across a broad spectrum of cancers is well established.27-29

Significant clinical evidence has also emerged to suggest that resveratrol may specifically target colon cancer.30

Spanish physiologists31 recently observed that resveratrol can accumulate at very high levels in the gut, making it an ideal agent for colon cancer prevention. They then treated human colorectal cancer cell cultures with resveratrol and found that not only does it suppress cell proliferation--resveratrol activates the so-called "cancer-executioner protein" caspase-3. This executioner protein in turn launches apoptosis (cell destruction), as confirmed by microscopic examination of the tissue. Remarkably, resveratrol inflicts no cellular damage to normal human tissue--a common and debilitating characteristic of conventional chemotherapy.

Researchers in Austria demonstrated that resveratrol blocks the reproductive cycle in colon cancer cells by neutralizing the enzymes they need in order to copy their genetic material--further confirmation of its role in cancer cell death.32

Other laboratories are finding still more pathways through which resveratrol prompts colon cancer to commit "cellular suicide."33 It miraculously takes aim at cancer's many targets, each one leading to cell death and destruction, without injury to healthy tissue--a life-extending trait unmatched by any conventional chemotherapy.

This makes resveratrol, along with curcumin, one of the most promising natural anticancer agents known to modern science.27 In fact, one fascinating recent study revealed that resveratrol at higher doses teams up with a commonly used chemotherapy drug called 5-fluorouracil to kill cancer cells synergistically. Acting together they become more lethal to cancer cells than either acting alone.

This holds out the possibility that, like curcumin, resveratrol may ultimately limit the toxic, debilitating side effects of standard chemotherapy drugs by lowering the required dose.34

Quercetin

Quercetin belongs to a class of potent antioxidants called flavonoids. These are what give apples their color. Onions, garlic, tea, red grapes, berries, broccoli, and leafy greens are also rich sources of quercetin.

It's well known to nutritional scientists as a potent free radical-scavenger.35 Quercetin also happens to possess a singular cancer-fighting feature: it can prevent cancer caused by chemicals. Its unique molecular structure enables it to block receptors on the cell surface that interact with carcinogenic chemical compounds. This makes it a perfect anticancer agent for the colon, where carcinogenic chemicals tend to accumulate.35

Researchers in Greece have also discovered that quercetin dramatically suppresses one particular cancer-causing gene in colon cells. This makes quercetin supplementation an ideal form of early prevention for individuals with a family history of colon cancer.36

Dutch scientists uncovered even more evidence of its cancer-preventive power at the genetic level. In an animal study, quercetin reduced "cancer gene" activity and increased "tumor-suppressor gene" activity in colon cells after only 11 weeks.37

In yet another promising animal study, scientists in South Carolina were able to halt the development of colon cancer at its earliest stage. During this stage, it emerges on the surface of the colon as clusters of abnormal, tube-like glands called aberrant crypt foci (ACF). Cancer-prone rats fed a diet high in quercetin10 underwent a four-fold reduction in the number of ACF compared to a control group. Similar research has yielded additional evidence of quercetin's capacity to reduce emerging ACF--a vital first step in preventing colon cancer from developing at all.38

As with curcumin and resveratrol, quercetin's multi-faceted chemopreventive profile means it can block cancer development at many different stages--furnishing modern oncology with a wide array of potentially chemopreventive mechanisms.

Green Tea and EGCG

Green tea is rich in polyphenol compounds called catechins. The best-known cancer-preventive agent among them is called epigallocatechin gallate, or EGCG.39 Like resveratrol, EGCG slows blood vessel formation in tumors (angiogenesis), effectively reducing the rate at which they can grow and spread. Consumption of green tea as a beverage may offer some measure of protection against colon cancer.40,41 However, the higher, more concentrated doses of EGCG available only in supplements may be required to get the maximum benefit.

Just last year, cancer researchers at Rutgers University put this idea to the test, supplementing rats with a standardized high-EGCG green tea extract for eight weeks after two weekly injections of a potent carcinogen.42 When the scientists then counted pre-cancerous ACF, they found significantly fewer in the animals given EGCG supplements than in control animals. Not only that--the ACF that did develop in supplemented animals were of lower grade than in controls--and supplemented animals showed higher rates of apoptosis.

EGCG has also shown promise in human trials. Cancer surgeons at the Robert Wood Johnson School of Medicine in New Jersey studied the effects of green tea on rectal lining cells in human volunteers.43 After just a single dose containing up to 1.8 grams of green tea solids, levels of an inflammatory mediator--the prostaglandin PGE2--fell substantially in the rectal cells from all subjects, with 10 of the 14 showing declines of at least 50%. Given the importance of inflammation in the cascade of events that lead to colorectal cancer, these effects underscore the key role green tea and its polyphenols play as potential chemopreventive agents.

The mounting clinical evidence of EGCG's multiple modes of action--and its minimal side effect profile--place this polyphenol alongside curcumin and resveratrol as one of nature's most potent allies in the battle against colon cancer.43-45

But the good news doesn't end with EGCG. In early 2008, German scientists discovered that green tea polyphenols generally deliver a direct preventive effect against colorectal cancer recurrence.46

Patients whose cancers or pre-malignant polyps had been surgically removed were given either a green tea-derived flavonoid mixture or a placebo, then followed for up to four years.

The contrast in rates of recurrence between the two groups was striking, to say the least--fully 47% of the placebo group experienced full cancer recurrence or recurrence of pre-cancerous adenomas, while only 7% of the supplemented group developed a single adenoma. As the researchers (under)stated, "Sustained long-term treatment with a flavonoid mixture could reduce the recurrence rate of colon neoplasia in patients with resected colon cancer."

Not surprisingly, a wide range of nutrients beyond polyphenols have outstanding cancer-preventive track records. Here are brief summaries of a few of them. Their active ingredients (as high-potency standardized extract) are readily available in supplement form.

Garlic

Both epidemiological and animal studies have conclusively illustrated the cancer-preventive effects of many of the compounds found in garlic.47-49 Aged garlic extract in particular acts not only as a potent antioxidant, but also:

A Japanese research group recently provided dramatic new data on aged garlic extract's power to prevent colorectal cancer in humans in a study of 37 patients diagnosed with colorectal adenomas--the precursors to cancer.56 Active group patients took aged garlic extract 2.4 mL per day (equivalent to about 720 mg powered extract57); control patients received a miniscule 0.16 mL per day; all patients had endoscopy done at the beginning of the study, and at 6 and 12 months.56 Control patients displayed the expected steady increase in number and size of adenomas--but in the supplemented group both adenoma number and size had been significantly reduced by the end of the 12-month period. The researchers concluded, "Aged garlic extract has multiple pathways to reduce cancer incidence and suppress its growth and proliferation."

As much as 7,200 mg/day of aged garlic powder has been consumed for up to six months without noted side effects.58

Ginger

Like garlic, ginger has been a mainstay of traditional medicine for more than 2,500 years. And, like garlic, ginger is now coming into its own in the eyes of Western medical scientists. Ginger's multiple chemopreventive benefits have been reported in a wide range of experimental models.59 Key compounds in ginger and its extracts limit the oxidative damage to cells caused by free radicals. They also lower levels of signaling molecules called cytokines, specifically those that provoke an inflammatory response. This dual mode of action results in increased cancer-destroying cell destruction.60,61 Some ginger components also increase the activity of vital enzymes that detoxify carcinogens present in the body.62,63

Indian researchers provided direct evidence of ginger's chemopreventive power in rats with chemically induced colon cancers in two recent studies.64,65 After injection with a potent carcinogen, animals were either supplemented with ginger or given normal diets. In both studies the incidence of cancers and the number of individual tumors was significantly reduced in the supplemented groups. The first study also detected lower levels of oxidative agents and higher levels of natural antioxidants in supplemented animals, while the second study further showed a decrease in the activity of bacterial enzymes that release intestinal toxins and damage the colon's natural protective mucous layer.

Cruciferous Vegetables and Sprouts

People who eat a diet rich in so-called cruciferous vegetables (the cabbage/broccoli/Brussels sprout family) are known to have lower rates of colon and other cancers.66,67 These vegetables and their sprouts contain key compounds and breakdown byproducts--including sulforaphane and indole-3-carbinol (I3C)--that exert potent antioxidant and anti-inflammatory effects in the body. They also specifically target and neutralize enzymes that would normally activate dietary carcinogens. In other words, they simultaneously keep cancer from developing and destroy emerging tumors in the early stages of the disease through cancer cell death.68-73

A number of animal studies demonstrate that supplementation with cruciferous vegetable extracts blocks cancerous changes in rat colons after the animals have already been exposed to dangerous, powerful carcinogens.67,73,74

Research on humans is just as promising. Several years ago, a group of researchers in Britain conducted a breakthrough study with enormous implications for human colon cancer chemo-prevention using cruciferous vegetables. They tested 20 healthy volunteers for carcinogens that can result from a diet high in red meat. The testing took place at the end of three distinct 12-day phases.

In the first phase, the study subjects ate no cruciferous vegetables at all. In the second phase, they ate 250 grams of broccoli and Brussels sprouts a day. In the third and final phase, they once again ate no cruciferous vegetables, in order to "wash out" any potential anticarcinogenic effect.75

Testing revealed that at the end of the second phase--during which they'd eaten broccoli and Brussels sprouts every day--the subjects' levels of detoxifying enzymes had risen dramatically, while urine tests showed a proportionate boost in detoxified carcinogenic molecules. In other words, broccoli and Brussels sprouts effectively neutralized dietary carcinogens in the body, rendering them harmless.

A remarkable 2008 study from England revealed that the cruciferous vegetable compound I3C intensifies the effect of the colon cancer chemotherapy drug oxaliplatin.76 Adding I3C helped researchers to kill off cancer cells at a six-fold higher rate compared to the chemotherapy drug alone.

This is more encouraging news. Like resveratrol, I3C may one day help physicians limit doses of toxic chemotherapy drugs like oxaliplatin and 5-fluorouracil--and offset the painful, debilitating side effects they inflict on cancer patients.

Eight Common Cancer-Fighting Nutrients

Vitamins and trace minerals act as powerful antioxidants, making them useful candidates for colon cancer chemoprevention. Numerous large-scale epidemiological studies point to the vitamins E and D, plus calcium, as potent colon cancer fighters.77-79 The data on vitamin D, for example, is excellent. Vitamin D reduces cancer cell proliferation in the colon--a necessary first step in cancer development.80

Interestingly, a recent study showed that vitamin E can make colon cancer cells more vulnerable to the lethal action of exisulind--a compound known to initiate programmed cancer cell death.81 Folate and vitamins B6 and B12 are also by expert consensus excellent chemoprevention candidates, owing to the critical role each plays in protecting healthy DNA.82

Selenium is an essential trace mineral with remarkable antioxidant properties. It's also one of nature's primary cancer-preventive nutrients.

Selenium activates a number of key enzymes in the body that keep cancer from developing.83 Preliminary studies have shown that people with higher selenium levels are at decreased risk of cancer.84 A study from the National Institutes of Health showed that high selenium reduced the risk of advanced colorectal adenomas, a cancer precursor, by nearly 25%! It afforded even greater protection in high-risk groups, including smokers.85

Conversely, people with colon cancer have significantly lower blood selenium levels.86 Fortunately selenium supplementation not only boosts serum selenium levels, but also ramps up the activity of vital cellular antioxidant systems that help prevent cancer from forming.87 There's also compelling evidence that selenium maximizes the anticancer effect of sulforaphane, the compound found in cruciferous vegetables, making the two a potent combination for bowel health.83

A growing body of epidemiological, clinical, and experimental evidence suggests that the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)--abundant in cold-water fish and fish oil--may also reduce the risk of colorectal cancer.88

Important findings from the Physicians' Health Study suggest that consuming fish and fish oils may protect against colorectal cancer. In this long-term prospective study of male physicians, greater intake of fish and omega-3 fatty acids was associated with a reduced risk of colon and rectal cancers.89

Experimental studies suggest that these omega-3 fatty acids may exert numerous anti-cancer effects, including regulating cell proliferation and apoptosis as well as fighting angiogenesis and metastasis. Additionally, some scientists have suggested that omega-3 acids may sensitize colon tumors to drugs that suppress the growth of abnormal tissue.90 Together, these findings point to an important role of omega-3 fatty acids from fish oil in averting colon cancer.

Summary

Colon cancer remains a serious threat to millions of men and women each year, and standard medical and surgical therapies to treat the disease are far from adequate. Because cancers develop in the colon as a direct result of its constant exposure to toxic chemicals and byproducts of digestion, a natural, nutrient-based approach to prevention makes good sense. Medical science is just beginning to gain a full appreciation of how nutrients can help avert this deadly disease. As renowned Italian surgeon and nutrition expert Dr. Duilio Divisi has written: "It has been estimated that 30-40% of all kinds of cancer can be prevented with a healthy lifestyle and dietary measures."91 Dr. Divisi remarked that in addition to the role of polyphenols described above, "Protective elements in a cancer-preventive diet include selenium, folic acid, vitamin B12, vitamin D, chlorophyll [abundant in leafy vegetables] and antioxidants… A diet drawn up according to the proposed guidelines could decrease the incidence of breast, colon-rectal, prostate and bronchogenic cancer."91

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